ID   VWA2_HUMAN              Reviewed;         755 AA.
AC   Q5GFL6; A1A5D4; B5MDJ8; Q6ZS39; Q6ZWJ7; Q708C5; Q70UZ8;
DT   23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2005, sequence version 1.
DT   27-MAR-2024, entry version 150.
DE   RecName: Full=von Willebrand factor A domain-containing protein 2;
DE   AltName: Full=A domain-containing protein similar to matrilin and collagen;
DE            Short=AMACO;
DE   AltName: Full=Colon cancer secreted protein 2;
DE            Short=CCSP-2;
DE   Flags: Precursor;
GN   Name=VWA2; Synonyms=AMACO;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-9.
RC   TISSUE=Placenta;
RX   PubMed=14506275; DOI=10.1074/jbc.m307794200;
RA   Sengle G., Kobbe B., Moergelin M., Paulsson M., Wagener R.;
RT   "Identification and characterization of AMACO, a new member of the von
RT   Willebrand factor A-like domain protein superfamily with a regulated
RT   expression in the kidney.";
RL   J. Biol. Chem. 278:50240-50249(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP   PROTEOLYTIC PROCESSING, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=15580307; DOI=10.1038/sj.onc.1208134;
RA   Xin B., Platzer P., Fink S.P., Reese L., Nosrati A., Willson J.K.V.,
RA   Wilson K., Markowitz S.;
RT   "Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological
RT   marker of colon neoplasia.";
RL   Oncogene 24:724-731(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS THR-9 AND
RP   GLY-131.
RC   TISSUE=Brain, and Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   VARIANT [LARGE SCALE ANALYSIS] ARG-137.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- SUBUNIT: Forms monomers and multimers. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q5GFL6; Q12933: TRAF2; NbExp=3; IntAct=EBI-10243723, EBI-355744;
CC       Q5GFL6-3; P26045: PTPN3; NbExp=3; IntAct=EBI-13451145, EBI-1047946;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q5GFL6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5GFL6-2; Sequence=VSP_028739;
CC       Name=3;
CC         IsoId=Q5GFL6-3; Sequence=VSP_028737, VSP_028738, VSP_028739;
CC   -!- TISSUE SPECIFICITY: Expression is generally absent in normal colon and
CC       other normal body tissues, but it is induced an average of 78-fold in
CC       Stage II, III, and IV colon cancers, as well as in colon adenomas and
CC       colon cancer cell lines. {ECO:0000269|PubMed:15580307}.
CC   -!- PTM: A 55 kDa form is produced by proteolytic cleavage.
CC       {ECO:0000269|PubMed:15580307}.
CC   -!- MISCELLANEOUS: May be used as a serological marker for colon neoplasia.
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DR   EMBL; AJ616914; CAE83814.1; -; mRNA.
DR   EMBL; AJ536328; CAD60276.1; -; mRNA.
DR   EMBL; AY572972; AAT77225.1; -; mRNA.
DR   EMBL; AY572973; AAT77226.1; -; Genomic_DNA.
DR   EMBL; AK122716; BAC85505.1; -; mRNA.
DR   EMBL; AK127756; BAC87116.1; -; mRNA.
DR   EMBL; AC005383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC022023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC128588; AAI28589.1; -; mRNA.
DR   CCDS; CCDS7589.2; -. [Q5GFL6-1]
DR   RefSeq; NP_001258975.1; NM_001272046.1. [Q5GFL6-1]
DR   RefSeq; NP_001307733.1; NM_001320804.1. [Q5GFL6-1]
DR   RefSeq; XP_011538059.1; XM_011539757.2.
DR   RefSeq; XP_016871669.1; XM_017016180.1. [Q5GFL6-3]
DR   AlphaFoldDB; Q5GFL6; -.
DR   SMR; Q5GFL6; -.
DR   BioGRID; 131091; 44.
DR   IntAct; Q5GFL6; 8.
DR   STRING; 9606.ENSP00000376708; -.
DR   GlyCosmos; Q5GFL6; 1 site, No reported glycans.
DR   GlyGen; Q5GFL6; 1 site.
DR   iPTMnet; Q5GFL6; -.
DR   PhosphoSitePlus; Q5GFL6; -.
DR   BioMuta; VWA2; -.
DR   DMDM; 74722595; -.
DR   jPOST; Q5GFL6; -.
DR   MassIVE; Q5GFL6; -.
DR   PaxDb; 9606-ENSP00000376708; -.
DR   PeptideAtlas; Q5GFL6; -.
DR   ProteomicsDB; 62826; -. [Q5GFL6-1]
DR   ProteomicsDB; 62827; -. [Q5GFL6-2]
DR   ProteomicsDB; 62828; -. [Q5GFL6-3]
DR   Antibodypedia; 46200; 112 antibodies from 22 providers.
DR   DNASU; 340706; -.
DR   Ensembl; ENST00000392982.8; ENSP00000376708.3; ENSG00000165816.13. [Q5GFL6-1]
DR   Ensembl; ENST00000603594.2; ENSP00000473752.2; ENSG00000165816.13. [Q5GFL6-3]
DR   GeneID; 340706; -.
DR   KEGG; hsa:340706; -.
DR   MANE-Select; ENST00000392982.8; ENSP00000376708.3; NM_001272046.2; NP_001258975.1.
DR   UCSC; uc001lbl.3; human. [Q5GFL6-1]
DR   AGR; HGNC:24709; -.
DR   CTD; 340706; -.
DR   DisGeNET; 340706; -.
DR   GeneCards; VWA2; -.
DR   HGNC; HGNC:24709; VWA2.
DR   HPA; ENSG00000165816; Tissue enhanced (stomach).
DR   MIM; 618281; gene.
DR   neXtProt; NX_Q5GFL6; -.
DR   OpenTargets; ENSG00000165816; -.
DR   PharmGKB; PA142670613; -.
DR   VEuPathDB; HostDB:ENSG00000165816; -.
DR   eggNOG; KOG3544; Eukaryota.
DR   GeneTree; ENSGT00940000159040; -.
DR   HOGENOM; CLU_008905_7_3_1; -.
DR   InParanoid; Q5GFL6; -.
DR   OMA; MWCSAAM; -.
DR   OrthoDB; 5299728at2759; -.
DR   PhylomeDB; Q5GFL6; -.
DR   TreeFam; TF318242; -.
DR   PathwayCommons; Q5GFL6; -.
DR   SignaLink; Q5GFL6; -.
DR   BioGRID-ORCS; 340706; 7 hits in 1135 CRISPR screens.
DR   ChiTaRS; VWA2; human.
DR   GeneWiki; VWA2; -.
DR   GenomeRNAi; 340706; -.
DR   Pharos; Q5GFL6; Tbio.
DR   PRO; PR:Q5GFL6; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q5GFL6; Protein.
DR   Bgee; ENSG00000165816; Expressed in thymus and 94 other cell types or tissues.
DR   GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR   GO; GO:0007161; P:calcium-independent cell-matrix adhesion; IBA:GO_Central.
DR   GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR   CDD; cd00053; EGF; 1.
DR   CDD; cd00054; EGF_CA; 1.
DR   CDD; cd01472; vWA_collagen; 1.
DR   Gene3D; 2.10.25.10; Laminin; 2.
DR   Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 3.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR002035; VWF_A.
DR   InterPro; IPR036465; vWFA_dom_sf.
DR   PANTHER; PTHR24020; COLLAGEN ALPHA; 1.
DR   PANTHER; PTHR24020:SF70; PH DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF00008; EGF; 2.
DR   Pfam; PF00092; VWA; 3.
DR   PRINTS; PR00453; VWFADOMAIN.
DR   SMART; SM00181; EGF; 2.
DR   SMART; SM00179; EGF_CA; 2.
DR   SMART; SM00327; VWA; 3.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   SUPFAM; SSF53300; vWA-like; 3.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 2.
DR   PROSITE; PS50234; VWFA; 3.
PE   1: Evidence at protein level;
KW   Alternative splicing; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..755
FT                   /note="von Willebrand factor A domain-containing protein 2"
FT                   /id="PRO_0000307362"
FT   DOMAIN          51..222
FT                   /note="VWFA 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   DOMAIN          296..333
FT                   /note="EGF-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          343..517
FT                   /note="VWFA 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   DOMAIN          531..705
FT                   /note="VWFA 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   DOMAIN          712..748
FT                   /note="EGF-like 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   SITE            267..268
FT                   /note="Cleavage"
FT   CARBOHYD        147
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        299..310
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        304..320
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        322..332
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        716..727
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        721..736
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        738..747
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   VAR_SEQ         1..304
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_028737"
FT   VAR_SEQ         305..332
FT                   /note="QNGGTCVPEGLDGYQCLCPLAFGGEANC -> MEAHVFQKDWTATSASARWP
FT                   LEGRLTVV (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_028738"
FT   VAR_SEQ         708..755
FT                   /note="EAKQPVNLCKPSPCMNEGSCVLQNGSYRCKCRDGWEGPHCENRFLRRP ->
FT                   GEWGNPHPQGCPHGRPSA (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_028739"
FT   VARIANT         9
FT                   /note="A -> T (in dbSNP:rs9664945)"
FT                   /evidence="ECO:0000269|PubMed:14506275,
FT                   ECO:0000269|PubMed:14702039"
FT                   /id="VAR_035418"
FT   VARIANT         131
FT                   /note="E -> G (in dbSNP:rs597371)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_035419"
FT   VARIANT         137
FT                   /note="L -> R (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036641"
FT   CONFLICT        76
FT                   /note="T -> A (in Ref. 3; BAC87116)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        428
FT                   /note="Q -> R (in Ref. 1; CAD60276)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   755 AA;  82012 MW;  E02B99335BE28BEC CRC64;
     MPPFLLLEAV CVFLFSRVPP SLPLQEVHVS KETIGKISAA SKMMWCSAAV DIMFLLDGSN
     SVGKGSFERS KHFAITVCDG LDISPERVRV GAFQFSSTPH LEFPLDSFST QQEVKARIKR
     MVFKGGRTET ELALKYLLHR GLPGGRNASV PQILIIVTDG KSQGDVALPS KQLKERGVTV
     FAVGVRFPRW EELHALASEP RGQHVLLAEQ VEDATNGLFS TLSSSAICSS ATPDCRVEAH
     PCEHRTLEMV REFAGNAPCW RGSRRTLAVL AAHCPFYSWK RVFLTHPATC YRTTCPGPCD
     SQPCQNGGTC VPEGLDGYQC LCPLAFGGEA NCALKLSLEC RVDLLFLLDS SAGTTLDGFL
     RAKVFVKRFV RAVLSEDSRA RVGVATYSRE LLVAVPVGEY QDVPDLVWSL DGIPFRGGPT
     LTGSALRQAA ERGFGSATRT GQDRPRRVVV LLTESHSEDE VAGPARHARA RELLLLGVGS
     EAVRAELEEI TGSPKHVMVY SDPQDLFNQI PELQGKLCSR QRPGCRTQAL DLVFMLDTSA
     SVGPENFAQM QSFVRSCALQ FEVNPDVTQV GLVVYGSQVQ TAFGLDTKPT RAAMLRAISQ
     APYLGGVGSA GTALLHIYDK VMTVQRGARP GVPKAVVVLT GGRGAEDAAV PAQKLRNNGI
     SVLVVGVGPV LSEGLRRLAG PRDSLIHVAA YADLRYHQDV LIEWLCGEAK QPVNLCKPSP
     CMNEGSCVLQ NGSYRCKCRD GWEGPHCENR FLRRP
//